Liston Group

Liston Group
Liston Group
Adrian Liston
Honorary Group Leader
Liston Group

Research Summary

The Liston laboratory works on regulatory T cells. These are a type of white blood cell that act to suppress the rest of the immune response, preventing spontaneous autoimmune disease and acting as a rheostat to control just how active our immune system is. The number of these cells in our blood goes up as we get old, which may contribute to the immune-suppressed state of older persons. We seek to understand these cells, using both patient material and mouse models, so that we can harness their power to fine-tune the immune system for healthy ageing.
 

Latest Publications

Kreisinger J, Dooley J, Singh K, Čížková D, Schmiedová L, Bendová B, Liston A, Moudra A Immunology

Microbiome research has gained much attention in recent years as the importance of gut microbiota in regulating host health becomes increasingly evident. However, the impact of radiation on the microbiota in the murine bone marrow transplantation model is still poorly understood. In this paper, we present key findings from our study on how radiation, followed by bone marrow transplantation with or without T cell depletion, impacts the microbiota in the ileum and caecum. Our findings show that radiation has different effects on the microbiota of the two intestinal regions, with the caecum showing increased interindividual variation, suggesting an impaired ability of the host to regulate microbial symbionts, consistent with the Anna Karenina principle. Additionally, we observed changes in the ileum composition, including an increase in bacterial taxa that are important modulators of host health, such as and . In contrast, radiation in the caecum was associated with an increased abundance of several common commensal taxa in the gut, including and . Finally, we found that high doses of radiation had more substantial effects on the caecal microbiota of the T-cell-depleted group than that of the non-T-cell-depleted group. Overall, our results contribute to a better understanding of the complex relationship between radiation and the gut microbiota in the context of bone marrow transplantation and highlight the importance of considering different intestinal regions when studying microbiome responses to environmental stressors.

+view abstract Frontiers in microbiology, PMID: 38903788

Burton OT, Bricard O, Tareen S, Gergelits V, Andrews S, Biggins L, Roca CP, Whyte C, Junius S, Brajic A, Pasciuto E, Ali M, Lemaitre P, Schlenner SM, Ishigame H, Brown BD, Dooley J, Liston A Immunology , Bioinformatics

The tissues are the site of many important immunological reactions, yet how the immune system is controlled at these sites remains opaque. Recent studies have identified Foxp3 regulatory T (Treg) cells in non-lymphoid tissues with unique characteristics compared with lymphoid Treg cells. However, tissue Treg cells have not been considered holistically across tissues. Here, we performed a systematic analysis of the Treg cell population residing in non-lymphoid organs throughout the body, revealing shared phenotypes, transient residency, and common molecular dependencies. Tissue Treg cells from different non-lymphoid organs shared T cell receptor (TCR) sequences, with functional capacity to drive multi-tissue Treg cell entry and were tissue-agnostic on tissue homing. Together, these results demonstrate that the tissue-resident Treg cell pool in most non-lymphoid organs, other than the gut, is largely constituted by broadly self-reactive Treg cells, characterized by transient multi-tissue migration. This work suggests common regulatory mechanisms may allow pan-tissue Treg cells to safeguard homeostasis across the body.

+view abstract Immunity, PMID: 38897202

Herppich S, Hoenicke L, Kern F, Kruse F, Smout J, Greweling-Pils MC, Geffers R, Burton OT, Liston A, Keller A, Floess S, Huehn J Immunology

Mucosal barrier integrity and pathogen clearance is a complex process influenced by both Th17 and Treg cells. Previously, we had described the DNA methylation profile of Th17 cells and identified Zinc finger protein (Zfp)362 to be uniquely demethylated. Here, we generated Zfp362 mice to unravel the role of Zfp362 for Th17 cell biology. Zfp362 mice appeared clinically normal, showed no phenotypic alterations in the T-cell compartment, and upon colonization with segmented filamentous bacteria, no effect of Zfp362 deficiency on Th17 cell differentiation was observed. By contrast, Zfp362 deletion resulted in increased frequencies of colonic Foxp3 Treg cells and IL-10 and RORγt Treg cell subsets in mesenteric lymph nodes. Adoptive transfer of naïve CD4 T cells from Zfp362 mice into Rag2 mice resulted in a significantly lower weight loss when compared with controls receiving cells from Zfp362 littermates. However, this attenuated weight loss did not correlate with alterations of Th17 cells but instead was associated with an increase of effector Treg cells in mesenteric lymph nodes. Together, these results suggest that Zfp362 plays an important role in promoting colonic inflammation; however, this function is derived from constraining the effector function of Treg cells rather than directly promoting Th17 cell differentiation.

+view abstract European journal of immunology, PMID: 37366299

Group Members

Adrian Liston

Honorary Group Leader

Magda Ali

PhD Student

Oliver Burton

Visiting Scientist

Amy Dashwood

PhD Student

James Dooley

Visiting Scientist

Vaclav Gergelits

Visiting Scientist

Ntombizodwa Makuyana

PhD Student

Omar Shabana

Visiting Student